title: Modulatory Effect of Gliadin Peptide 10-mer on Epithelial Intestinal CACO-2 Cell Inflammatory Response.
abstract: Celiac Disease (CD) is a chronic inflammatory enteropathy, triggered in genetically susceptible individuals by dietary gluten. Gluten is able to elicit proliferation of specific T cells and secretion of inflammatory cytokines in the small intestine. In this study we investigated the possibility that p10-mer, a decapeptide from durum wheat (QQPQDAVQPF), which was previously shown to prevent the activation of celiac peripheral lymphocytes, may exert an inhibitory effect on peptic-tryptic digested gliadin (PT-Gly)-stimulated intestinal carcinoma CACO-2 cells. In these cells, incubated with PT-Gly or p31-43 α-gliadin derived peptide in the presence or in the absence of p10-mer, IRAK1 activation and NF-kB, ERK1/2 and p38 MAPK phosphorylation were measured by immunoblotting, Cyclooxigenase 2 (COX-2) activity by PGE-2 release assay, and production of cytokines in the cell supernatants by ELISA. Our results showed that pre-treatment of CACO-2 cells with p10-mer significantly inhibited IRAK1 activation and NF-kB, ERK1/2 and p38 MAPK phosphorylation, as well as COX-2 activity (i.e. PGE-2 release) and production of the IL-6 and IL-8 pro-inflammatory cytokines, induced by gliadin peptides. These findings demonstrate the inhibitory effect of the p10-mer peptide on inflammatory response in CACO-2 cells. The results of the present study show that this p10-mer peptide can modulate "in vitro" the inflammatory response induced by gliadin peptides, allowing to move towards new therapeutic strategies. Turning off the inflammatory response, may in fact represent a key target in the immunotherapy of celiac disease.
authors.affiliation: Department of Experimental Medicine, Sapienza University, Rome, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Capozzi
authors.forename: Olimpia
authors.initials: O
authors.lastname: Vincentini
authors.forename: Pietro
authors.initials: P
authors.lastname: Gizzi
authors.forename: Alessandra
authors.initials: A
authors.lastname: Porzia
authors.forename: Agostina
authors.initials: A
authors.lastname: Longo
authors.forename: Cristina
authors.initials: C
authors.lastname: Felli
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Mattei
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Mainiero
authors.forename: Marco
authors.initials: M
authors.lastname: Silano
authors.forename: Maurizio
authors.initials: M
authors.lastname: Sorice
authors.forename: Roberta
authors.initials: R
authors.lastname: Misasi
mesh_terms: D000595:Amino Acid Sequence; D018938:Caco-2 Cells; D016207:Cytokines / Q000096:biosynthesis; D005903:Gliadin / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007249:Inflammation / Q000517:prevention & control*; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology*; D010446:Peptide Fragments / Q000494:pharmacology*
chemical_list: D016207:Cytokines; D010446:Peptide Fragments; D005903:Gliadin